Structural evaluation of the SUMOlation activation in the human malaria parasite Plasmodium falciparum

Abstract

Reversible post-translational modification of proteins by ubiquitin (Ub) and ubiquitin-like modifiers (Ubls) serves an essential regulatory mechanism for fundamental cellular processes such as cell cycle progression, DNA damage repair, nucleocytoplasmic transport, transcription, and chromatin remodelling. Protein modification by small ubiquitin-like modifiers (SUMOs) is mediated by the conjugation of the respected Ub/Ubls to target proteins proceeds through the sequential interactions and activities of parallel cascades of enzymes that are structurally and mechanistically related. E1 enzymes initiate SUMO conjugation cascades by catalysing the adenosine triphosphate (ATP)-dependent activation and transfer of their cognate SUMO to E2-conjugating enzymes, which then function with an array of E3 ligases to catalyse the formation of an isopeptide bond linking the SUMO to target proteins. SUMO E1 is a modular, multi-domain ~110kDa heterodimer comprised of SUMO-activating enzyme 1 (Sae1) and 2 (Sae2) subunits that harbour two catalytic activities required for activation of SUMO. Within this proposal we would like to shed light on SUMO activation process of the human malaria parasite Plasmodium falciparum by structural analysis. (AU)